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Protein

Calcitonin gene-related peptide type 1 receptor

Gene

CALCRL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.By similarity1 Publication

GO - Molecular functioni

  • adrenomedullin receptor activity Source: UniProtKB
  • calcitonin gene-related peptide receptor activity Source: Ensembl
  • calcitonin receptor activity Source: InterPro
  • G-protein coupled receptor activity Source: ProtInc
  • protein transporter activity Source: UniProtKB

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
  • angiogenesis Source: UniProtKB
  • calcium ion transport Source: UniProtKB
  • cAMP biosynthetic process Source: UniProtKB
  • cell surface receptor signaling pathway Source: InterPro
  • cellular response to sucrose stimulus Source: UniProtKB
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  • heart development Source: Ensembl
  • negative regulation of inflammatory response Source: Ensembl
  • negative regulation of smooth muscle contraction Source: Ensembl
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • protein transport Source: UniProtKB
  • receptor internalization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000064989-MONOMER.
ReactomeiR-HSA-418555. G alpha (s) signalling events.
R-HSA-419812. Calcitonin-like ligand receptors.

Protein family/group databases

TCDBi9.A.14.4.12. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcitonin gene-related peptide type 1 receptor
Short name:
CGRP type 1 receptor
Alternative name(s):
Calcitonin receptor-like receptor
Gene namesi
Name:CALCRL
Synonyms:CGRPR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:16709. CALCRL.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 146ExtracellularSequence analysisAdd BLAST124
Transmembranei147 – 166Helical; Name=1Sequence analysisAdd BLAST20
Topological domaini167 – 173CytoplasmicSequence analysis7
Transmembranei174 – 193Helical; Name=2Sequence analysisAdd BLAST20
Topological domaini194 – 213ExtracellularSequence analysisAdd BLAST20
Transmembranei214 – 236Helical; Name=3Sequence analysisAdd BLAST23
Topological domaini237 – 253CytoplasmicSequence analysisAdd BLAST17
Transmembranei254 – 273Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini274 – 289ExtracellularSequence analysisAdd BLAST16
Transmembranei290 – 313Helical; Name=5Sequence analysisAdd BLAST24
Topological domaini314 – 336CytoplasmicSequence analysisAdd BLAST23
Transmembranei337 – 354Helical; Name=6Sequence analysisAdd BLAST18
Topological domaini355 – 366ExtracellularSequence analysisAdd BLAST12
Transmembranei367 – 388Helical; Name=7Sequence analysisAdd BLAST22
Topological domaini389 – 461CytoplasmicSequence analysisAdd BLAST73

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • lysosome Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72W → A: Strongly reduced affinity for adrenomedullin. 1 Publication1
Mutagenesisi92F → A: Strongly reduced affinity for adrenomedullin. 1 Publication1
Mutagenesisi121W → A: Strongly reduced affinity for adrenomedullin. 1 Publication1

Organism-specific databases

DisGeNETi10203.
PharmGKBiPA26033.

Chemistry databases

ChEMBLiCHEMBL3798.

Polymorphism and mutation databases

DMDMi226693507.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000001281123 – 461Calcitonin gene-related peptide type 1 receptorAdd BLAST439

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi48 ↔ 74
Disulfide bondi65 ↔ 105
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi88 ↔ 127
Glycosylationi118N-linked (GlcNAc...)Sequence analysis1
Glycosylationi123N-linked (GlcNAc...)Sequence analysis1
Modified residuei420PhosphoserineBy similarity1
Modified residuei445PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ16602.
PeptideAtlasiQ16602.
PRIDEiQ16602.

PTM databases

iPTMnetiQ16602.
PhosphoSitePlusiQ16602.

Expressioni

Tissue specificityi

Predominantly expressed in the lung and heart.

Gene expression databases

BgeeiENSG00000064989.
CleanExiHS_CALCRL.
ExpressionAtlasiQ16602. baseline and differential.
GenevisibleiQ16602. HS.

Organism-specific databases

HPAiHPA008070.

Interactioni

Subunit structurei

Heterodimer of CALCRL and RAMP3 (By similarity). Heterodimer of CALCRL and RAMP1 or CALCRL and RAMP2.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CALCAP068812EBI-962878,EBI-962928
RAMP2O608956EBI-962878,EBI-9009040

Protein-protein interaction databases

BioGridi115498. 4 interactors.
DIPiDIP-37674N.
IntActiQ16602. 4 interactors.
STRINGi9606.ENSP00000376177.

Chemistry databases

BindingDBiQ16602.

Structurei

Secondary structure

1461
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi33 – 35Combined sources3
Helixi36 – 54Combined sources19
Beta strandi60 – 62Combined sources3
Beta strandi63 – 65Combined sources3
Beta strandi78 – 87Combined sources10
Beta strandi90 – 92Combined sources3
Beta strandi99 – 105Combined sources7
Turni115 – 117Combined sources3
Helixi125 – 127Combined sources3
Helixi129 – 131Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AQFX-ray2.60B23-136[»]
3N7PX-ray2.80A/B/C/J23-133[»]
3N7RX-ray2.90A/B23-133[»]
3N7SX-ray2.10A/B23-133[»]
4RWFX-ray1.76A31-116[»]
4RWGX-ray2.44A/B/C31-114[»]
ProteinModelPortaliQ16602.
SMRiQ16602.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16602.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
HOVERGENiHBG102129.
InParanoidiQ16602.
KOiK04577.
OrthoDBiEOG091G027C.
PhylomeDBiQ16602.
TreeFamiTF315710.

Family and domain databases

InterProiIPR003287. GCPR_2_calcitonin_rcpt_fam.
IPR017981. GPCR_2-like.
IPR003289. GPCR_2_CGRP1_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01351. CGRPRECEPTOR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q16602-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKKCTLNFL VLLPFFMILV TAELEESPED SIQLGVTRNK IMTAQYECYQ
60 70 80 90 100
KIMQDPIQQA EGVYCNRTWD GWLCWNDVAA GTESMQLCPD YFQDFDPSEK
110 120 130 140 150
VTKICDQDGN WFRHPASNRT WTNYTQCNVN THEKVKTALN LFYLTIIGHG
160 170 180 190 200
LSIASLLISL GIFFYFKSLS CQRITLHKNL FFSFVCNSVV TIIHLTAVAN
210 220 230 240 250
NQALVATNPV SCKVSQFIHL YLMGCNYFWM LCEGIYLHTL IVVAVFAEKQ
260 270 280 290 300
HLMWYYFLGW GFPLIPACIH AIARSLYYND NCWISSDTHL LYIIHGPICA
310 320 330 340 350
ALLVNLFFLL NIVRVLITKL KVTHQAESNL YMKAVRATLI LVPLLGIEFV
360 370 380 390 400
LIPWRPEGKI AEEVYDYIMH ILMHFQGLLV STIFCFFNGE VQAILRRNWN
410 420 430 440 450
QYKIQFGNSF SNSEALRSAS YTVSTISDGP GYSHDCPSEH LNGKSIHDIE
460
NVLLKPENLY N
Length:461
Mass (Da):52,929
Last modified:April 14, 2009 - v2
Checksum:iAF98E55E5454767C
GO

Sequence cautioni

The sequence BAF84319 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144L → Q in BAF84319 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0548228N → Y.1 PublicationCorresponds to variant rs698577dbSNPEnsembl.1
Natural variantiVAR_04945316F → L.Corresponds to variant rs13391909dbSNPEnsembl.1
Natural variantiVAR_049454274R → I.Corresponds to variant rs34010553dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76380 mRNA. Translation: AAC41994.1.
U17473 mRNA. Translation: AAA62158.1.
AY389506 mRNA. Translation: AAQ91332.1.
AK291630 mRNA. Translation: BAF84319.1. Different initiation.
AK292998 mRNA. Translation: BAF85687.1.
AC007319 Genomic DNA. Translation: AAY14806.1.
AC074020 Genomic DNA. Translation: AAY14996.1.
CCDSiCCDS2293.1.
PIRiJC2477.
RefSeqiNP_001258680.1. NM_001271751.1.
NP_005786.1. NM_005795.5.
UniGeneiHs.470882.
Hs.744587.

Genome annotation databases

EnsembliENST00000392370; ENSP00000376177; ENSG00000064989.
ENST00000409998; ENSP00000386972; ENSG00000064989.
ENST00000410068; ENSP00000387190; ENSG00000064989.
GeneIDi10203.
KEGGihsa:10203.
UCSCiuc002upv.6. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76380 mRNA. Translation: AAC41994.1.
U17473 mRNA. Translation: AAA62158.1.
AY389506 mRNA. Translation: AAQ91332.1.
AK291630 mRNA. Translation: BAF84319.1. Different initiation.
AK292998 mRNA. Translation: BAF85687.1.
AC007319 Genomic DNA. Translation: AAY14806.1.
AC074020 Genomic DNA. Translation: AAY14996.1.
CCDSiCCDS2293.1.
PIRiJC2477.
RefSeqiNP_001258680.1. NM_001271751.1.
NP_005786.1. NM_005795.5.
UniGeneiHs.470882.
Hs.744587.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AQFX-ray2.60B23-136[»]
3N7PX-ray2.80A/B/C/J23-133[»]
3N7RX-ray2.90A/B23-133[»]
3N7SX-ray2.10A/B23-133[»]
4RWFX-ray1.76A31-116[»]
4RWGX-ray2.44A/B/C31-114[»]
ProteinModelPortaliQ16602.
SMRiQ16602.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115498. 4 interactors.
DIPiDIP-37674N.
IntActiQ16602. 4 interactors.
STRINGi9606.ENSP00000376177.

Chemistry databases

BindingDBiQ16602.
ChEMBLiCHEMBL3798.

Protein family/group databases

TCDBi9.A.14.4.12. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiQ16602.
PhosphoSitePlusiQ16602.

Polymorphism and mutation databases

DMDMi226693507.

Proteomic databases

PaxDbiQ16602.
PeptideAtlasiQ16602.
PRIDEiQ16602.

Protocols and materials databases

DNASUi10203.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000392370; ENSP00000376177; ENSG00000064989.
ENST00000409998; ENSP00000386972; ENSG00000064989.
ENST00000410068; ENSP00000387190; ENSG00000064989.
GeneIDi10203.
KEGGihsa:10203.
UCSCiuc002upv.6. human.

Organism-specific databases

CTDi10203.
DisGeNETi10203.
GeneCardsiCALCRL.
HGNCiHGNC:16709. CALCRL.
HPAiHPA008070.
MIMi114190. gene.
neXtProtiNX_Q16602.
PharmGKBiPA26033.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
HOVERGENiHBG102129.
InParanoidiQ16602.
KOiK04577.
OrthoDBiEOG091G027C.
PhylomeDBiQ16602.
TreeFamiTF315710.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000064989-MONOMER.
ReactomeiR-HSA-418555. G alpha (s) signalling events.
R-HSA-419812. Calcitonin-like ligand receptors.

Miscellaneous databases

EvolutionaryTraceiQ16602.
GeneWikiiCALCRL.
GenomeRNAii10203.
PROiQ16602.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064989.
CleanExiHS_CALCRL.
ExpressionAtlasiQ16602. baseline and differential.
GenevisibleiQ16602. HS.

Family and domain databases

InterProiIPR003287. GCPR_2_calcitonin_rcpt_fam.
IPR017981. GPCR_2-like.
IPR003289. GPCR_2_CGRP1_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01351. CGRPRECEPTOR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCALRL_HUMAN
AccessioniPrimary (citable) accession number: Q16602
Secondary accession number(s): A8K6G5
, A8KAD3, Q53S02, Q53TS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 14, 2009
Last modified: November 2, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.